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Stone analysis Stone analysis Mostafa Sabry Abdullah Demonstrator Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University Definition: Stone formation is a genetic, nutritional or environmental disease Incidence: Recent studies indicate that over 10% of adult males suffering from urinary stone at least one Mechanism of stone formation: Urinary stones are always formed of substances that normally excreted in the urine These substances for unknown causes are supersaturated to pass their solubility products leading to their precipitation and formation of crystals that bind together to form stones Alternative names include: Renal Lithiasis Renal Calculi Nephrolithiasis (Kidney Stone Disease) Depending on its location in the urinary tract it is called : Kidney Stone Ureteric Stone Bladder Stone Urethral Stone Classification of stones: Stones may be classified according to two methods: A According to number of components: a) Simple stones: contain only single constituent e.g Ca oxalate b) Mixed stones: contain two or more constituent e.g Ca oxalate+ Ca& Mg phosphate B According to type of components: 1) Ca Oxalate stones: (the most common in Egypt) 2) Ca Phosphate stones 3) Ca Carbonate stones 4) Mg Ammonium Phosphate stones 5) Uric acid stones: 4-10 % 6) Cystine stones: < 1% 7) Xanthin stones: very rare 8) Struvite Stones 9) Foreign body stones: formed of foreign body that introduced into the body from outside Kidney Stone Occurrence in When they form type Population Calcium oxalate 80 % when urine is acidic or alkaline Calcium 0% when urine is alkaline (high pH) Uric acid 5-10 % when urine is persistently acidic Struvite 10-15 % infections in the kidney Cystine 0% rare genetic disorder phosphate Calcium stones Struvite Stones Uric Acid stones Cystine Stones Factors affecting stone formation:1- Change urine pH: Bacteria Urea NH3 pH stone 2- Vitamins disturbances: e.g - Exss Vit D Ca absorption Ca stones - Exss Vit C oxalate stones - Vit A Roughness of epithelial cells lining to the urinary tract ppt of crystals crystal formation 3- Hormonal disturbance : e.g Hyperparathyroidism Ca2+ stones 4- uric acid level uric acid stones 5- mucoprotein: which act as a cement material to bind crystals stones Risk factors for stone formation Renal risk factor 1- Infections, 2- Obstructions, 3- Parasitic infections, as:- schistosomiasis 4- Congenital anomalies Pre-urinary risk factors: A) Intrinsic: 1-Hereditary: 2- Age: 3- Sex: Mechanical factors : A) Intrinsic: 1-Hereditary: Renal tubular acidosis :; Primary hyperoxaluria; Cystinuria; Hyperuricosuria; Absorptive hypercalciuria: this is the most common Cushing syndrome 4- Occupation: There is a higher incidence of stone in sedentary workers (in the armed force, office personal have a higher risk than active units such as the royal marine) 5- Water: a) Amount: chronic dehydration stone disease b) Hot climate c) Hot occupation d) Low fluid intake: patients whose 24h urinary volumes are less than 1400 ml show an increased recurrence rate e) Composition: stone formation is higher in soft water areas than in hard water areas 6- Infection stones: Chronic infections in the urinary tract can cause renal calculi that are Struvite: magnesium ammonium phosphate (Mg NH4.6H2O;) and Carbonate appetite: (Ca10PO4.6CO3) The most common found in stone patients are Proteus and Pseudomonas Inhibitors of stone formation: a) Ions: citrate, magnesium, and pyrophosphate b) Larger molecules: Glycosaminoglycans (GAGs): Nephrocalcin: Complexers: Glycosaminoglycans (GAGs): They are polysaccharides chains of repeating disaccharides derived by degradation of high molecular weight proteoglycans; GAG excretion is greater in male subjects, rising post- prandially and at night ; excretion rises by 50% in summer; GAGs inhibit calcium oxalate crystallization Nephrocalcin: It is a recently isolated γ- carboxy-glutamic acid-containing protein ; it inhibits calcium oxalate crystallization and may be structurally abnormal or deficient in some stone patients Complexers: Specific charged ions combine with potential crystalline components to form soluble complexes reducing the free ionic concentration: Anions such as citrate , phosphate , and sulphate complex calcium Cations such as magnesium complex oxalate Promoters of stone formation: Tamm- Horsfall protein and the organic matrix The composition of the urine diurnal variation The times associated with the highest supersaturation occur between and 10 a.m and between and 10 p.m Meals cause variations, especially in the concentration of calcium The highest excretion of oxalate and urate occurs early in the morning Tamm- Horsfall protein It is the matrix of urinary casts derived from the secretion of renal tubular cells When this protein is concentrated at low pH, it forms a gel act as a constitutive inhibitor of calcium crystallization in renal fluids,provide defense against urinary tract infections Inhibitors Citrate Magnesium Pyrophosphate Glycosaminogly can • Nephrocalcin • High urine volume • • • • Promoters Calcium Sodium Oxalate Urate Low urine pH Tamm- Horsfall protein Low urine volume • • • • • • •